19-52029018-C-T

Variant names:

• chr19-52029018-C-T
• rs2288884
• ENST00000597952.1:c.-217+838G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000597952.1(ZNF614):​c.-217+838G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,172 control chromosomes in the GnomAD database, including 2,184 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (2184 hom., cov: 32)
• Consequence: ZNF614 ENST00000597952.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.514
• Publications: 19 publications found

Genes affected

ZNF614 (HGNC:24722): (zinc finger protein 614) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

LOC112268244 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000597952.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF614	ENST00000597952.1	TSL:3	c.-217+838G>A		intron	N/A	ENSP00000469809.1	M0QYG4
	ENSG00000297250	ENST00000746485.1		n.249-1881C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22369 AN: 152054 Hom.: 2181 Cov.: 32

Gnomad AFR AF: 0.0534

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.157

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.147 AC: 22396 AN: 152172 Hom.: 2184 Cov.: 32 AF XY: 0.152 AC XY: 11305 AN XY: 74372

African (AFR) AF: 0.0534 AC: 2219 AN: 41534

American (AMR) AF: 0.193 AC: 2946 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 413 AN: 3470

East Asian (EAS) AF: 0.377 AC: 1951 AN: 5174

South Asian (SAS) AF: 0.291 AC: 1402 AN: 4826

European-Finnish (FIN) AF: 0.165 AC: 1743 AN: 10578

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11211 AN: 67990

Other (OTH) AF: 0.159 AC: 337 AN: 2116

Alfa AF: 0.163 Hom.: 5110

Bravo AF: 0.144

Asia WGS AF: 0.324 AC: 1122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.4
DANN	Benign	0.68
PhyloP100		-0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2288884;

hg19: chr19-52532271;